HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 280, Issue 40, 33785-33791, October 7, 2005

This Article Full Text Full Text (PDF) All Versions of this Article: 280/40/33785    most recent M505742200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hiniker, A. Articles by Bardwell, J. C. A. Search for Related Content PubMed PubMed Citation Articles by Hiniker, A. Articles by Bardwell, J. C. A. Social Bookmarking                      What's this?

Copper Stress Causes an in Vivo Requirement for the Escherichia coli Disulfide Isomerase DsbC^*

Annie Hiniker1, Jean-Francois Collet¶, and James C. A. Bardwell||2

From the Program in Cellular and Molecular Biology, the Medical Scientist Training Program, and the ^||Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, Michigan 48109-1048 and the ^¶Christian de Duve Institute of Cellular Pathology, Universite Catholique de Louvain, 1200 Brussels, Belgium

In Escherichia coli, the periplasmic disulfide oxidoreductase DsbA is thought to be a powerful but nonspecific oxidant, joining cysteines together the moment they enter the periplasm. DsbC, the primary disulfide isomerase, likely resolves incorrect disulfides. Given the reliance of protein function on correct disulfide bonds, it is surprising that no phenotype has been established for null mutations in dsbC. Here we demonstrate that mutations in the entire DsbC disulfide isomerization pathway cause an increased sensitivity to the redox-active metal copper. We find that copper catalyzes periplasmic disulfide bond formation under aerobic conditions and that copper catalyzes the formation of disulfide-bonded oligomers in vitro, which DsbC can resolve. Our data suggest that the copper sensitivity of dsbC^– strains arises from the inability of the cell to rearrange copper-catalyzed non-native disulfides in the absence of functional DsbC. Absence of functional DsbA augments the deleterious effects of copper on a dsbC^– strain, even though the dsbA^– single mutant is unaffected by copper. This may indicate that DsbA successfully competes with copper and forms disulfide bonds more accurately than copper does. These findings lead us to a model in which DsbA may be significantly more accurate in disulfide oxidation than previously thought, and in which the primary role of DsbC may be to rearrange incorrect disulfide bonds that are formed during certain oxidative stresses.

Received for publication, May 26, 2005 , and in revised form, August 5, 2005.

^* This work was supported by National Institutes of Health Grant GM064662 (to J. C. A. B.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ A National Defense Science and Engineering Graduate Fellow.

² To whom correspondence should be addressed: Dept. of Molecular, Cellular, and Developmental Biology, 4007 Krauss Natural Sciences Bldg., 830 North University, Ann Arbor, MI, 48109-1048. Tel.: 734-764-8028; Fax: 734-647-0884; E-mail: jbardwel{at}umich.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				S. J. Coulthurst, K. S. Lilley, P. E. Hedley, H. Liu, I. K. Toth, and G. P. C. Salmond DsbA Plays a Critical and Multifaceted Role in the Production of Secreted Virulence Factors by the Phytopathogen Erwinia carotovora subsp. atroseptica J. Biol. Chem., August 29, 2008; 283(35): 23739 - 23753. [Abstract] [Full Text] [PDF]

				E. Matuszewska, J. Kwiatkowska, D. Kuczynska-Wisnik, and E. Laskowska Escherichia coli heat-shock proteins IbpA/B are involved in resistance to oxidative stress induced by copper Microbiology, June 1, 2008; 154(6): 1739 - 1747. [Abstract] [Full Text] [PDF]

				L. Fontaine and P. Hols The Inhibitory Spectrum of Thermophilin 9 from Streptococcus thermophilus LMD-9 Depends on the Production of Multiple Peptides and the Activity of BlpGSt, a Thiol-Disulfide Oxidase Appl. Envir. Microbiol., February 15, 2008; 74(4): 1102 - 1110. [Abstract] [Full Text] [PDF]

				J. Messens, J.-F. Collet, K. Van Belle, E. Brosens, R. Loris, and L. Wyns The Oxidase DsbA Folds a Protein with a Nonconsecutive Disulfide J. Biol. Chem., October 26, 2007; 282(43): 31302 - 31307. [Abstract] [Full Text] [PDF]

				S. Monchy, M. A. Benotmane, P. Janssen, T. Vallaeys, S. Taghavi, D. van der Lelie, and M. Mergeay Plasmids pMOL28 and pMOL30 of Cupriavidus metallidurans Are Specialized in the Maximal Viable Response to Heavy Metals J. Bacteriol., October 15, 2007; 189(20): 7417 - 7425. [Abstract] [Full Text] [PDF]

				S. Quan, I. Schneider, J. Pan, A. Von Hacht, and J. C. A. Bardwell The CXXC Motif Is More than a Redox Rheostat J. Biol. Chem., September 28, 2007; 282(39): 28823 - 28833. [Abstract] [Full Text] [PDF]

				A. Hiniker, G. Ren, B. Heras, Y. Zheng, S. Laurinec, R. W. Jobson, J. A. Stuckey, J. L. Martin, and J. C. A. Bardwell Laboratory evolution of one disulfide isomerase to resemble another PNAS, July 10, 2007; 104(28): 11670 - 11675. [Abstract] [Full Text] [PDF]

				L. Macomber, C. Rensing, and J. A. Imlay Intracellular Copper Does Not Catalyze the Formation of Oxidative DNA Damage in Escherichia coli J. Bacteriol., March 1, 2007; 189(5): 1616 - 1626. [Abstract] [Full Text] [PDF]

				A. Hiniker, D. Vertommen, J. C. A. Bardwell, and J.-F. Collet Evidence for Conformational Changes within DsbD: Possible Role for Membrane-Embedded Proline Residues. J. Bacteriol., October 1, 2006; 188(20): 7317 - 7320. [Abstract] [Full Text] [PDF]